Functional and Genomic Analysis of Rouxiella badensis SER3 as a Novel Biocontrol Agent of Fungal Pathogens.
In recent decades, various bacterial species have been characterized as biocontrol agents for plant crop diseases; however, only a few genera have been predominantly reported in the literature. Therefore, the identification of new antagonists against phytopathogens is essential for boosting sustainable food production systems. In this study, we evaluated the role of strain SER3 from the recently discovered Rouxiella badensis as a biocontrol agent. SER3 was isolated from the phyllosphere of decaying strawberry fruit (Fragaria × ananassa) and showed different grades of antagonism against 20 fungal pathogens of berries, based on confrontation assays, due to the action of its diffusible and volatile compounds. These fungal pathogens were isolated from decayed strawberry, blackberry, and blueberry fruit and were characterized through internal transcribed spacer (ITS) sequencing and homology searches, exhibiting similarity with well-known postharvest pathogens such as Botrytis, Fusarium, Geotrichum, Mucor, Penicillium, Alternaria, and Botryosphaeria. Koch's postulates were confirmed for most pathogens by reinfecting berry fruit. SER3 showed good capacity to inhibit the growth of Botrytis cinerea and Fusarium brachygibbosum in strawberry fruit, affecting mycelial development. To gain better understanding of the genetic and metabolic capacities of the SER3 strain, its draft genome was determined and was found to comprise a single chromosome of 5.08 Mb, 52.8% G + C content, and 4,545 protein-coding genes. Phylogenetic analysis indicated that the SER3 strain is affiliated with the R. badensis species, with an average nucleotide identity >96% and a genome-to-genome distance >70%. A comparison of the genomic properties of R. badensis SER3 and other close bacterial relatives showed several genes with potential functions in biocontrol activities, such as those encoding siderophores, non-ribosomal peptide synthetases, and polyketide synthases. This is the first study to demonstrate a novel role of the recently discovered R. badensis species (and any other species of the genus Rouxiella) as a biocontrol agent against postharvest fungal pathogens.


Diagnosis of osteoarticular tuberculosis: multi-targeted loop-mediated isothermal amplification assay versus multiplex PCR.
Aim: Diagnosis of osteoarticular tuberculosis (OATB) is quite challenging and there is an urgent need to design a prompt and precise diagnostic test. Methods: We developed a multi-targeted loop-mediated isothermal amplification (LAMP) assay using mpt64 (Rv1980c) and pstS1 (Rv0934) targets for the detection of Mycobacterium tuberculosis in OATB patients. Results: The sensitivities of 100 and 82.4% were obtained in confirmed (n = 10) and suspected (n = 57) OATB cases, respectively by multi-targeted LAMP with a specificity of 96.9% (n = 33). Moreover, the sensitivities attained by multi-targeted LAMP in total OATB cases were significantly higher (p < 0.05-0.01) than multiplex PCR (mpt64 + pstS1) and GeneXpert assay. Conclusion: Our LAMP is simple, reliable and cost-effective method, which may develop into an attractive diagnostic kit for early detection of OATB cases.


Prevalence and genetic diversity of simian immunodeficiency virus infection in wild-living red colobus monkeys (Piliocolobus badius badius) from the Taï forest, Côte d'Ivoire SIVwrc in wild-living western red colobus monkeys.
Numerous African primates are infected with simian immunodeficiency viruses (SIVs). It is now well established that the clade of SIVs infecting west-central African chimpanzees (Pan troglodytes troglodytes) and western gorillas (Gorilla gorilla gorilla) represent the progenitors of human immunodeficiency virus type 1 (HIV-1), whereas HIV-2 results from different cross-species transmissions of SIVsmm from sooty mangabeys (Cercocebus atys atys). We present here the first molecular epidemiological survey of simian immunodeficiency virus (SIVwrc) in wild-living western red colobus monkeys (Piliocolobus badius badius) which are frequently hunted by the human population and represent a favourite prey of western chimpanzees (Pan troglodytes verus). We collected faecal samples (n=88) and we assessed individual discrimination by microsatellite analyses and visual observation. We tested the inferred 53 adult individuals belonging to two neighbouring habituated groups for presence of SIVwrc infection by viral RNA (vRNA) detection. We amplified viral polymerase (pol) (650 bp) and/or envelope (env) (570 bp) sequences in 14 individuals, resulting in a minimal prevalence of 26% among the individuals sampled, possibly reaching 50% when considering the relatively low sensitivity of viral RNA detection in faecal samples. With a few exceptions, phylogenetic analysis of pol and env sequences revealed a low degree of intragroup genetic diversity and a general viral clustering related to the social group of origin. However, we found a higher intergroup diversity. Behavioural and demographic data collected previously from these communities indicate that red colobus monkeys live in promiscuous multi-male societies, where females leave their natal group at the sub-adult stage of their lives and where extra-group copulations or male immigration have been rarely observed. The phylogenetic data we obtained seem to reflect these behavioural characteristics. Overall, our results indicate that wild-living red colobus represent a substantial reservoir of SIVwrc. Moreover, because of their frequent association with other monkey species, the predation pressure exerted by chimpanzees (Pan troglodytes verus) and by poachers around and inside the park, simian to simian and simian to human SIVwrc cross-species transmission cannot be excluded.


A critical review of maximal androgen blockade for advanced prostate cancer.
For over 60 years, the primary treatment for metastatic prostate cancer has been androgen ablation. Medical or surgical castration eliminates most, but not all androgen production, with a small contribution still coming from the adrenal gland. When castration fails, secondary adrenalectomy can provide some palliative benefit. However, the development of oral antiandrogens has offered an opportunity to simultaneously interfere with androgen produced in the testes and adrenal gland. Combined androgen blockade (CAB) has been investigated extensively with conflicting results. Based on a critical review of these studies, CAB still appears to offer the longest duration of survival and should continue to be offered as an option to men with metastatic disease.


Optimization of biological phosphorus removal from contaminated sediments with phosphate-solubilizing microorganisms.
This study focused on the characteristics of phosphate-solubilizing microorganisms (PSMs) which can be applied for the removal of phosphorus from sediments to prevent eutrophication of lakes or ponds. A PSM isolated from rhizospheric soil and temporarily identified as Burkholderia glathei (MB 14) produced gluconate and acetate using glucose as a carbon source and its metabolic activity caused the pH of the liquid medium to decrease as low as 4.4. The molar ratio of solubilized PO4(3-)-P to total organic acids, gluconate and acetate, in the liquid medium was 1:2, which was lower than the theoretical molar ratio of 1:3 using Ca3(PO4)2 as a model phosphorus compound. In addition, biological PO4(3-)-P solubilization with MB 14 was more efficient than the direct addition of equivalent acid to the liquid medium. These results indirectly suggest that organic acids chelate Ca2+ during solubilization of PO4(3-)-P. The growth conditions for MB 14 that produced the maximum PO4(3-)-P solubilization were carbon sources of 8 g/l of glucose and 2 g/l of sucrose, and 0.1 g/l of arginine as a nitrogen source under an anoxic environment. The PSM species, MB 14, grown under these conditions was applied to treat contaminated dredged sediments in a bioslurry reactor. In 9 d, MB 14 solubilized 34.5% of total phosphorus in the contaminated dredged sediments.


Disorder-driven doping activation in organic semiconductors.
Conductivity doping of organic semiconductors is an essential prerequisite for many organic devices, but the specifics of dopant activation are still not well understood. Using many-body simulations that include Coulomb interactions and dopant ionization/de-ionization events explicitly we here show significant doping efficiency even before the electron affinity of the dopant exceeds the ionization potential of the organic matrix (p-doping), similar to organic salts. We explicitly demonstrate that the ionization of weak molecular dopants in organic semiconductors is a disorder-, rather than thermally induced process. Practical implications of this finding are a weak dependence of the ionized dopant fraction on the electron affinity of the dopant, and an enhanced ionization of the weak dopants upon increasing dopant molar fraction. As a result, strategies towards dopant optimization should aim for presently neglected goals, such as the binding energy in host-dopant charge-transfer states being responsible for the number of mobile charge carriers. Insights into reported effects are provided from the analysis of the density of states, where two novel features appear upon partial dopant ionization. The findings in this work can be used in the rational design of dopant molecules and devices.


Assessment of extracellular fluid volume and fluid status in hemodialysis patients: current status and technical advances.
The assessment of extracellular fluid volume (ECV) and fluid status is both important and challenging in hemodialysis patients. Extracellular fluid is distributed in two major sub-compartments: interstitial fluid and plasma. A variety of methods are used to assess the ECV, with tracer dilution techniques considered gold standard. However, ECV defined as the distribution space of bromide, sodium, chloride, and ferrocyanide appears to be larger than the distribution volume of inulin and sucrose, suggesting a partial distribution into the intracellular volume. Relative blood volume monitoring, measurement of inferior vena cava diameter by ultrasound and biochemical markers are indirect methods, which do not reflect the ECV and fluid status accurately. Bioimpedance spectroscopy (BIS) techniques enable assessment of ECV and intracellular volume. Currently, BIS appears to be the most practical method for assessing ECV volume and fluid status in dialysis patients.


Endodontics and diabetes: association versus causation.
Endodontic Medicine has gained more attention and is becoming a more important issue in Endodontics. As an example, more than one hundred articles on this topic have been published in the last eight years. Several of these studies have found an association between endodontic variables, that is the prevalence of apical periodontitis, the prevalence of root canal treatment (RCT) and the outcome of RCT assessed as root filled teeth (RFT) with radiolucent periapical lesions (RPL) or non-retained RFT, and several systemic diseases, such as diabetes, cardiovascular disease, smoking habits, osteoporosis, inherited coagulopaties, biological medications, low birth weight or physical fitness. However, the demonstration of association does not prove by itself the existence of a cause-effect relationship. Two variables can be related statistically to each other without either variable directly affecting the values of the other thus resulting in a non-causal relationship. Causality is assumed when one variable is shown to contribute to the development of the other, and its removal is shown to reduce the frequency of disease. Therefore, once a significant statistical association has been found between two variables, it is necessary to exclude the presence of bias, which would imply that the association is artefactual, and to analyse if the causation criteria defined by Hill (Proceedings of the Royal Society of Medicine 1965; 58: 295-300) are fulfilled to establish a causal relationship. Only if they are satisfied, can it be concluded that the association is causal. The aim of this study was to analyse the difference between association and causation, applying the criteria of causality to the specific case of the association between endodontic disease and diabetes mellitus.


Phenotypical analysis of the Lactobacillus rhamnosus GG fimbrial spaFED operon: surface expression and functional characterization of recombinant SpaFED pili in Lactococcus lactis.
A noticeable genomic feature of many piliated Gram-positive bacterial species is the presence of more than one pilus-encoding operon. Paradigmatically, the gut-adapted Lactobacillus rhamnosus GG strain contains two different fimbrial operons in its genome. However, whereas one of these operons (called spaCBA) is encoding for the functionally mucus-/collagen-binding SpaCBA pilus, for the other operon (called spaFED) any native expression of the SpaFED-called pili is still the subject of some uncertainty. Irrespective of such considerations, we decided it would be of relevance or interest to decipher the gross structure of this pilus type, and as well assess its functional capabilities for cellular adhesion and immunostimulation. For this, and by following the approach we had used previously to explicate the immuno-properties of SpaCBA pili, we constructed nisin-inducible expression clones producing either wild-type or SpaF pilin-deleted surface-assembled L. rhamnosus GG SpaFED pili on Lactococcus lactis cells. Using these piliated lactococcal constructs, we found that the pilin-polymerized architecture of a recombinant-produced SpaFED pilus coincides with sequence-based functional predictions of the related pilins, and in fact is prototypical of those other sortase-dependent pilus-like structures thus far characterized for piliated Gram-positive bacteria. Moreover, we confirmed that among the different pilin subunits encompassing spaFED operon-encoded pili, the SpaF pilin is a main adhesion determinant, and when present in the assembled structure can mediate pilus binding to mucus, certain extracellular matrix proteins, and different gut epithelial cell lines. However, somewhat unexpectedly, when recombinant SpaFED pili are surface-attached, we found that they could not potentiate the existing lactococcal cell-induced immune responses so elicited from intestinal- and immune-related cells, but rather instead, they could dampen them. Accordingly, we have now provided the first phenotypical description of a spaFED pilus operon, and with that furthered the functional understanding of surface piliation for a particular gut-commensalic genre of piliated Gram-positive bacteria.


An efficient sampling algorithm for variational Monte Carlo.
We propose a new algorithm for sampling the N-body density mid R:Psi(R)mid R:(2)R(3N)mid R:Psimid R:(2) in the variational Monte Carlo framework. This algorithm is based upon a modified Ricci-Ciccotti discretization of the Langevin dynamics in the phase space (R,P) improved by a Metropolis-Hastings accept/reject step. We show through some representative numerical examples (lithium, fluorine, and copper atoms and phenol molecule) that this algorithm is superior to the standard sampling algorithm based on the biased random walk (importance sampling).


Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis.
To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions. We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data. Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole. Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.


Urinary Tract Infection and Bacteriuria in Pregnancy.
Bacteriuria during pregnancy may be classified as asymptomatic bacteriuria, infections of the lower urinary tract (cystitis), or infections of the upper urinary tract (pyelonephritis). Lower tract bacteriuria is associated with an increased risk of developing pyelonephritis in pregnancy, which is itself associated with adverse maternal and fetal outcomes. Pregnant women should be screened for the presence of bacteriuria early in pregnancy. All bacteriuria in pregnancy should be treated, and antimicrobial choice in pregnancy should reflect safety for both the mother and the fetus. After treatment of bacteriuria, patients should be followed closely due to risk of recurrent bacteriuria.


Isoenzyme pattern and subcellular localization of hexokinases in human breast cancer and nonpathological breast tissue.
Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions used were cytosol, mitochondria and microsomes. A comparison of two methods for detecting HK activity was made, yielding different results regarding HK II and HK III. A method based on the ability of NADPH to fluoresce in UV gave a constant pattern of HK isoenzymes. In non-pathological breast tissue, only HK I was seen, i.e. in the cytosol and the microsomal fractions. HK I was also seen in all fractions of the cancers, but another more anodal band of HK I, as well as HK II and HK III, consistently appeared in the cytosol fractions. The more commonly used staining technique with tetrazolium dye revealed HK II in 45% and HK III in 50% of the samples. The pattern of HK isoenzymes in the cancers was the same irrespective of estrogen and progesterone cytosolic receptor contents and the histology of the tumors. The fluorescence method is, therefore, much more sensitive than the tetrazolium technique for detecting HK activity after electrophoresis and could explain difference in results obtained by various laboratories.


Effect of rajyoga meditation on chronic tension headache.
Chronic tension-type headache (CTTH) is the most common type of headache with no truly effective treatment. This study was designed to correlate the additive effect of meditation on CTTH patients receiving medical treatment. 50 patients (aged 18-58 years) presenting with a clinical diagnosis of CCTH, were divided in 2 groups. Group 1 (n=30) received 8 lessons and practical demonstration of Brahmakumaris spiritual based meditation known as Rajyoga meditation for relaxation therapy, in addition to routine medical treatment (analgesics and muscle relaxants). Group 2 (n=20) patients received analgesics and muscle relaxants twice a day but no relaxation therapy in the form of meditation. Both groups were followed up for 8 weeks period. The parameters studied were severity, frequency and duration of CCTH, and their headache index calculated. Patients in both groups showed a highly significant reduction in headache variables (P<0.001) after 8 weeks. But the percentage of patients showing highly significant relief in severity of headache, duration & frequency in Group 1 was 94%, 91% and 97% respectively whereas in Group 2 it was 36%, 36% and 49% respectively. Headache relief as calculated by headache index was 99% in Group 1 as compared to 51% in Group 2. Even Short term spiritual based relaxation therapy (Rajyoga meditation) was highly effective in causing earlier relief in chronic tension headache as measured by headache parameter.


Antioxidant isoflavones in Osage orange, Maclura pomifera (Raf.) Schneid.
Recent findings that many human chronic diseases are associated with oxidative stresses have instigated the search for dietary antioxidants. Many phytochemicals, particularly phenolic compounds, have been found to possess strong antioxidant activity and reduce the risks of those diseases. Isoflavones, a special phenolic group found in soybean, have been found to act as antioxidants in some model systems. This study investigated the isoflavone content in a unique nonedible tree fruit, Osage orange [Maclura pomifera (Raf.) Schneid], and methods for the extraction, identification, and quantification of the two major isoflavones, osajin and pomiferin, were developed. The ethyl acetate extract contained 25.7% osajin and 36.2% pomiferin, and the two isoflavones were at 9.5 g kg(-1) of fresh Osage orange. Two model systems, FRAP and beta-CLAMS, were used to measure the antioxidant activity of these two isoflavones. Pomiferin was found to be a strong antioxidant in both systems, comparable to the antioxidant vitamins C and E and the synthetic antioxidant BHT. Osajin and the two soybean isoflavones (genistein and daidzein) showed no antioxidant activity. Although the Osage orange fruit is not a food source, it is considered to be safe and, therefore, a potentially good source of an antioxidant nutraceutical and functional food ingredient.


Effects of curcumin on restoration and improvement of microvasculature characteristic in diabetic rat's choroid of eye.
To investigate the effect ofcurcumin on microvasculature changes in STZ-induced diabetic rat' choroid ofeye. Male rats were divided into three groups: control (C) Diabetic rats were induced by streptozotocin (STZ) (60 mg/kg BW) (DM) diabetic rats treated with curcumin (DMC) (200 mg/kg BW). After 8 weeks of experiments, microvasculature changes of rat's choroid were studied under vascular corrosion cast technique with scanning electron microscope (SEM). There were pathology and destruction of choroid microvasculature of DM group that revealed reduced and shrunken sizes of large and small blood vessels, compared with control group; long posterior ciliary arteries (LPCAs) (C = 113.70 +/- 1.38, DM = 83.53 +/- 2.70, DMC = 109.64 +/- 3.41 microm), choroid arteries (C = 94.97 +/- 2.79, DM = 59.36 +/- 2.61, DMC = 80.31 +/- 3.73 microm), vortex veins (C = 74.11 +/- 3.24, DM = 46.71 +/- 2.56, DMC = 64.66 +/- 3.60 microm), and Choriocapillaris (choroidal capillaries) (C = 13.61 +/- 0.62, DM = 4.46 +/- 0.24, DMC = 9.96 +/- 0.70 microm), respectively. In DM group, LPCAs and Choroid arteries were tortuous and showed shrinkage. Vortex veins became narrow. Choriocapillaris showed the pathological characteristics of vascular lesions including of shrinkage, constriction, microaneurysm and blind ending. Fascinatingly, Choroid microvasculature of the eye in curcumin treated group developed into regenerate and repaired conditions with healthy and normal characteristics. Efficiency of curcumin treatment beneficially repaired and regenerated the redevelopment of choroid's microvascular complications of eye in 8-week experiments. Potential treatment with curcumin in diabetes has demonstrated in a meaningful way the therapeutic consequences in the improvement and recovery of choroidal blood vessels in eye pathology ofdiabetic rats.


Ocular toxoplasmosis: clinical features and prognosis of 154 patients.
To ascertain the clinical features, visual outcome, and recurrence rates of ocular toxoplasmosis (OT) in a large series of patients. To determine the efficacy of various treatment strategies and identify the patients at risk of visual loss. Retrospective noncomparative observational case series. One hundred fifty-four consecutive patients with active lesions of OT (first attack and/or recurrence) were identified in a cohort of 1300 consecutive patients with uveitis. Mean follow-up was 5.8 years. A review of the medical records of 154 patients with active OT. Patients were subdivided according to clinical and laboratory criteria. Numerous variables were compared per patient and group, including age and gender distribution, onset and course of infection, clinical ocular features, laboratory data, therapeutic strategies and their outcomes, number of recurrences, complications, final visual acuity, and features associated with poor visual outcome. Primary retinal lesions were observed in 28% and a combination of active lesions and old retinochoroidal scars in 72% of the patients at first presentation to the ophthalmologist. Mean age at first presentation with an active OT lesion was 29.5 years. Patients with primary OT were older than those with a combination of active lesions and old scars (P < 0.001). Serologic characteristics of the acute phase of systemic infection were found in 11% of the patients. Ocular involvement in these patients was associated with advanced age at onset (P < 0.001) and was characterized by severe intraocular inflammation. Most (82%) of the patients with serologic characteristics of the acute phase of systemic infection had primary lesions (compared with 23% of OT in the chronic phase of systemic infection; P < 0.001). Extensive retinal lesions were more frequently observed during the acute phase of systemic infection (P = 0.02) and in patients with primary OT (P < 0.04). Recurrences, which developed in 79% of all patients followed for more than 5 years, were located predominantly in previously affected eyes (with old scars) in contrast to the sporadic cases of recurrence in the healthy contralateral eye (P < 0.0001). Standard short-term therapeutic modalities had no effect on visual outcome or future recurrence rates. Legal blindness in one or both eyes was confirmed for 24% of the patients. Blindness of both eyes was more frequent in patients with congenital OT (P < 0.001). Risk factors for visual loss included congenital infection, OT manifesting during the acute phase of systemic infection, central location and/or extensive retinal lesions, and the administration of corticosteroids without a shield of antiparasitic drugs. Legal blindness in at least one eye developed in 24% of the patients with OT. Recurrences, which developed in 79% of the patients with long-term follow-up, were located predominantly in eyes with toxoplasmic scars. Various short-term therapeutic modalities had no effect on visual outcomes or future recurrence rates, with the exception of a poor visual outcome for patients who received corticosteroids without a shield of antiparasitic drugs.


[Treatment of intertrochanteric fracture of femur with closed reduction of proximal femoral anti rotation intramedullary nail in supine position].
To investigate the effect and feasibility of closed reduction and internal fixation with PFNA in the treatment of intertrochanteric fracture of femur in the supine position without traction bed. From June 2014 to March 2018, 45 patients with intertrochanteric fracture of femur who were treated and followed up were analyzed retrospectively. There were 21 males and 24 females, with an average age of 67.4 years (43 to 92 years);18 cases on the left side and 27 on the right side. According to Evans Jensen classification, there were 7 patients of type Ⅱ, 17 patients of type Ⅲ, 16 patients of type Ⅳ and 5 patients of type Ⅴ. The time from injury to operationwas 2 to 6 days. The operation time, blood loss and fracture healing, closing time, postoperative complications and Harris score of hip joint were recorded. The operation time of 45 patients was 35 to 80 min, with an average of 52.6 min;the intraoperative bleeding volume was 40 to 110 ml, with an average of 68.7 ml;the hospitalization time was 6 to 11 days, with an average of 8.4 days;the follow up time was 12 to 18 months, with an average of 14.7 months;the internal fixation of 2 patients failed, and 43 patients achieved bony healing;the deep vein thrombosis of the lower extremity in the perioperative period was 1 case, and the inferior vena cava filter was inserted;the internal fixation of 2 patients was cut out, and the hip was renovated. The incidence of complications was 8.9%(4 / 45). At the final follow up, Harris score of hip joint was 56 to 95 (81.30±8.40), including excellent 15 cases, good 26 cases, fair 2 cases and poor 2 cases. It is safe and feasible to treat intertrochanteric fracture of femur with closed reduction and anti rotation intramedullary nailing under the bed without traction in a supine position. It has the advantages of small trauma and low complications, and the clinical effect is satisfactory. It is worth popularizing and using in basic hospitals.


Necrotizing fasciitis in a renal transplant patient.
We have described a 28-year-old diabetic woman who had necrotizing fasciitis of the perineum three years after receiving a living related renal transplant. The diagnosis of necrotizing fasciitis was made early and she was referred to a tertiary care center where she received radical perineal debridement and aggressive medical and surgical follow-up. Necrotizing fasciitis in a transplant patient is rare; review of the literature shows few cases and no survivors. Our patient has returned to a normal life despite continuation of all immunosuppressive therapy throughout the entire hospital course. In addition, she had a good cosmetic result despite the large necrotic perineal infection. Her survival can be attributed to early diagnosis and referral, immediate and extensive debridement, and aggressive protein replacement.


Advancing the role of nursing in the medical home model.
The patient-centered primary care model has been positioned to improve patient outcomes, enhance patient satisfaction, and reduce health care costs. The role of nursing in this care transformation is evident in ProvenHealth Navigator-one of the organization's primary care models. ProvenHealth Navigator incorporates primary care practice redesign, including team-delivered care, as the foundation for its model. Case managers, as one of the components of the care team, have demonstrated their value in reducing fragmentation, enhancing care transitions, and coordinating care for the most complex patients.Combining the strengths of a clinical delivery system with the population management expertise of a health plan, ProvenHealth Navigator capitalizes on the strengths of an integrated health care system to stratify the population, enhance access, optimize outpatient treatment, provide near real-time reporting, and deploy additional disease/case management resources for those most in need of additional health care services. Operational since 2006, ProvenHealth Navigator has been associated with significant reductions in all-cause admissions, readmissions, and total cost of care. In addition, quality indicators for chronic conditions and preventive care improved and patient and clinician satisfaction is high. Optimizing the role of primary care teams and focusing on population management services provides one method of improving quality and reducing costs thus increasing health care value.


[Determinant factors and conduct in post-accident with biological material among pre-hospital professionals].
This transversal study was carried out with a multiprofessional team in the pre-hospital care in Minas Gerais, Brazil. It aimed to estimate the incidence of occupational accidents by exposure to biological material and post-accidents conductsta. Descriptive analysis and logistic regression were used. Incidence of accidents was 19.8%: 39,1% perforating-cutting materials and 56.5% body fluids. Doctors (33.3%) and drivers (24.0%) were most involved. Inadequate subsequent measures were highly prevalent: no medical assessment (69.6%), no work accident communication issued (91.3%), no measures (52.2%) and no serological follow-up (52.2%). Variables associated with accidents were: age >31 years old (OR = 3,02; IC95%: 1,25 - 7,33; p = 0,014) and working in basic support units (OR = 5,36; IC95%: 1,51 19,08; p = 0,010). The implementation of post-accidents protocols is suggested in order to reduce accidents and under-notification, and increase post-accident follow-up.


Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites.
Environmental conditions in early life permanently alter the development of glucocorticoid receptor gene expression in the hippocampus and hypothalamic-pituitary-adrenal responses to acute or chronic stress. In part, these effects can involve an activation of ascending serotonergic pathways and subsequent changes in the expression of transcription factors that might drive glucocorticoid receptor expression in the hippocampus. This paper summarizes the evidence in favor of these pathways as well as recent studies describing regulatory targets within the chromatin structure of the promoter region of the rat hippocampal glucocorticoid receptor gene.


On the use of Pantopaque in renal cysts.
Local Pantopaque instillation receives continued support in the urologic and radiologic literature as a method for treating benign renal cysts. If benign renal cysts are a common lesion with an exceedingly small complication rate, what is the rationale for such treatment with a potentially hazardous substance?


Inulin stimulates NO synthesis via activation of PKC-alpha and protein tyrosine kinase, resulting in the activation of NF-kappaB by IFN-gamma-primed RAW 264.7 cells.
Inulin, an active component of Chicorium intybus root, has been shown to stimulate the growth of bifidobacteria, and inhibit colon carcinogenesis. NO mediates a number of the host-defense functions of activated macrophages, including antimicrobial and tumoricidal activity. We examined the effect of inulin on the synthesis of NO in RAW 264.7 cells. Inulin alone had no effect, whereas inulin with IFN-gamma synergistically increased the NO production and inducible NO synthase (iNOS) expression in RAW 264.7 cells. Synergy between IFN-gamma and inulin was mainly dependent on inulin-induced TNF-alpha secretion. Also, protein kinase C (PKC)-alpha was involved in the inulin-induced NO production. Inulin-mediated NO production was inhibited by the protein tyrosine kinase (PTK) inhibitor, tyrphostin AG126. Since iNOS gene transcriptions have been shown to be under the control of the NF-kappaB/Rel family of transcription factors, we assessed the effect of inulin on NF-kappaB/Rel using an EMSA. Inulin produced strong induction of NF-kappaB/Rel binding, whereas AP-1 binding was slightly induced in RAW 264.7 cells. Inulin stimulated phosphorylation and degradation of IkappaB-alpha. These results suggest that in IFN-gamma-primed RAW 264.7 cells inulin might stimulate NO synthesis via activation of PKC-alpha and PTK, resulting in the activation of NF-kappaB.


GSTT1 gene deletion is associated with lung cancer in Mexican patients.
Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking. We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.


Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('IRESSA'), a selective epidermal growth factor receptor tyrosine kinase inhibitor.
Overexpression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types, including head and neck squamous cell carcinomas (HNSCC). Recent laboratory experiments have demonstrated that high EGFR levels correlate with increased tumor resistance to radiation. This study investigated the relationship between EGFR expression levels and radiosensitivity in 5 HNSCC cell lines (HSC2, HSC3, HSC4, SCC25, and Ca9-22) and whether treatment with ZD1839 ('Iressa'), a selective EGFR-tyrosine kinase inhibitor (TKI), would improve tumor cell response to radiotherapy. ZD1839 suppressed the growth of HNSCC cell lines in a dose- and time-dependent manner. Radiosensitivity of these HNSCC cell lines, assessed by a clonogenic survival assay, differed greatly and the expression of EGFR varied. EGFR expression levels (EGFR numbers/cell) correlated with increased tumor resistance to radiation (f[x]= 4.54 X, R2 = 0.715; f[x]: EGFR numbers/cell, X: radiosensitivity; D10). Following exposure of the HNSCC cells to 1.0 microM ZD1839 and radiation (0-10 Gy), greater than additive growth inhibitory effects were observed. These results suggest that ZD1839 could enhance tumor radiosensitivity and inhibit tumor growth after radiation, indicating that this combination could have clinical potential in the treatment of patients with head and neck cancer.


The Effect of Abdominal Muscle Activation Techniques on Trunk and Lower Limb Mechanics During the Single-Leg Squat Task in Females.
Females suffer 4 to 6 times more noncontact anterior cruciate ligament (ACL) injuries than males due to neuromuscular control deficits of the hip musculature leading to increases in hip adduction angle, knee abduction angle, and knee abduction moment during dynamic tasks such as single-leg squats. Lateral trunk displacement has been further related to ACL injury risk in females, leading to the incorporation of core strength/stability exercises in ACL preventative training programs. However, the direct mechanism relating lateral trunk displacement and lower limb ACL risk factors is not well established. To assess the relationship between lateral trunk displacement and lower limb measures of ACL injury risk by altering trunk control through abdominal activation techniques during single-leg squats in healthy females. Interventional study setting: movement and posture laboratory. A total of 13 healthy females (21.3 [0.88] y, 1.68 [0.07] m, and 58.27 [5.46] kg). Trunk position and lower limb kinematics were recorded using an optoelectric motion capture system during single-leg squats under differing conditions of abdominal muscle activation (abdominal hollowing, abdominal bracing, and control), confirmed using surface electromyography. Lateral trunk displacement, peak hip adduction angle, peak knee abduction angle/moment, and average muscle activity from bilateral internal oblique, external oblique, and erector spinae muscles. No differences were observed for peak lateral trunk displacement, peak hip adduction angle, or peak knee abduction angle/moment. Abdominal hollowing and bracing elicited greater muscle activation than the control condition, and bracing was greater than hollowing in 4 of 6 muscles recorded. The lack of reduction in trunk, hip, and knee measures of ACL injury risk during abdominal hollowing and bracing suggests that these techniques alone may provide minimal benefit in ACL injury prevention training.


Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes.
Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs). Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography. GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression. Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.


Interaction of ketamine with mu2 opioid receptors in SH-SY5Y human neuroblastoma cells.
Ketamine is known to interact with opioid receptors. However, because this agent does not produce opioid-like respiratory depression, it might not interact with mu(2) opioid receptors. Therefore, we have studied the interaction of ketamine with mu(2) opioid receptors expressed in SH-SY5Y cells. SH-SY5Y cells (passage 70-80) were used to obtain ketamine dose-response curves for inhibition of 0.4 nM [(3)H][D-Ala(2),MePhe(4),Gly(ol)(5)] enkephalin (DAMGO) binding to mu(2) opioid receptors and of forskolin (1 microM)-stimulated cyclic AMP (cAMP) formation. Ketamine displaced [(3)H]DAMGO binding in SH-SY5Y cells with a K(i) of 12.1 microM. However, this concentrations did not inhibit forskolin-stimulated cAMP formation, although at supraclinical concentrations, significant inhibition was observed with an estimated IC(50) of 700 microM. The present study indicates that a clinically relevant concentration of ketamine interacts with mu(2) opioid receptors. However, no agonist activity was observed.


Effect of the growth of nano-sized Pd particle in 1 wt% Pd/gamma-Al2O3 catalyst on the complete oxidation of volatile organic compounds.
The effect of growth of nano-sized Pd particle on the catalytic activity of 1 wt% Pd/gamma-Al2O3 catalyst were examined to obtain the complete oxidation of volatile organic compounds (VOCs: toluene, xylene). Fresh and used forms of 1 wt% Pd/gamma-Al2O3 catalysts were characterized by using X-ray photoelectron microscopy (XPS), Transmission electron microscopy (TEM), and Brunauer Emmett Teller (BET) surface area analyses. Catalytic activity tests revealed that the conversion of VOCs increased with the lapse of reaction time at certain reaction temperature. The results of the instrumental analyses and the catalytic performance indicated that the conversion of VOCs was highly dependent on the growth of nano-sized Pd particle in the catalyst.


GATA Binding Protein 3 Is a Direct Target of Kruppel-Like Transcription Factor 7 and Inhibits Chicken Adipogenesis.
Kruppel-like transcription factor 7 (KLF7) is a negative regulator of adipogenesis, however, its precise mechanism is poorly understood. Our previous KLF7 ChIP-seq analysis showed that one of the KLF7 binding peaks was present upstream of GATA binding protein 3 (GATA3) in chicken preadipocytes. In the present study, we identified GATA3 as a target of KLF7. Overexpression analysis showed KLF7 markedly enhanced the endogenous expression of GATA3 in the immortalized chicken preadipcyte cell line (ICP2), and the luciferase reporter assay showed that KLF7 overexpression increased the reporter gene activity of the cloned upstream region (-5285/-4336 relative to the translation initiation codon ATG) of GATA3 in ICP2 and DF1 cells, and mutation of the putative KLF7 binding site abolished the promotive effect of KLF7 overexpression on the reporter gene activity of the cloned GATA3 upstream region. ChIP-qPCR further demonstrated that KLF7 directly bound to the GATA3 upstream region. Gene expression analysis showed that GATA3 mRNA expression in abdominal adipose tissue was significantly higher in lean chicken line than in the fat line at 2, 3, and 6 weeks of age. In addition, GATA3 mRNA expression markedly decreased during the preadipocyte differentiation. Furthermore, a functional study showed that GATA3 overexpression inhibited the differentiation of the ICP2 cells. Taken together, our results demonstrated that KLF7 inhibits chicken adipogenesis, at least in part through direct upregulation of GATA3.


Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer.
The study was undertaken to evaluate the diagnostic and prognostic value of plasma osteopontin (OPN) in comparison to bone markers as well as the relationships between the markers and clinico-pathological factors in prostate cancer (PCa) patients. OPN and the bone markers carboxyterminal-telopeptide of type I collagen, bone-specific alkaline phosphatase (bALP), and aminoterminal-propeptide of type I procollagen (PINP) were measured in 90 PCa patients with and without bone metastases, 35 patients with benign prostatic hyperplasia, and 29 healthy men. OPN and bone markers were significantly elevated in patients with bone metastases compared to the other groups. Significant correlations were found between all four-bone markers (r(s) = 0.43-0.79, all P < 0.01). OPN correlated with tumor grade (r(s) = 0.23, P < 0.05). In receiver-operating characteristics (ROC) analyses, OPN and bone markers were effective in distinguishing PCa patients with and without bone metastases showing areas under the curve (AUC) between 0.80 and 0.88 (all P < 0.001). OPN had an AUC of 0.85 that increased in combination with bALP up to 0.93 providing at the point with the highest diagnostic accuracy both a sensitivity and specificity of about 90%. Kaplan-Meier analyses and Cox proportional hazards regression models showed decreased survival of patients with high OPN and bone marker levels, while only high OPN and PINP were independent negative prognostic factors for PCa-related death. OPN alone or in combination with bone markers is useful as diagnostic marker in the detection of bone metastases and as prognosticator in the survival prediction in PCa patients.


Structure of the alpha-fetoprotein gene in the mouse.
The mouse alpha-fetoprotein mRNA is the product of a single-copy gene whose mRNA coding sequences are represented discontinuously in the genome. Several EcoRI genomic fragments which contain portions of the alpha-fetoprotein gene have been cloned using the EK2 vector lambda gt WES . lambda B. In addition, a mouse genomic library has been screened to obtain a 15.75-kilobase segment of DNA that includes more than 85% of the alpha-fetoprotein coding sequence. Analyses by restriction endonuclease mapping and electron microscopy showed that the mRNA sequence is interrupted by at least 11 intervening sequences which occupy 90% of the cloned DNA.


Gestational Age-Dependent Abundance of Human Placental Transporters as Determined by Quantitative Targeted Proteomics.
Some women take medication during pregnancy to address a variety of clinical conditions. Because of ethical and logistical concerns, it is impossible to determine fetal drug exposure, and therefore fetal risk, during pregnancy. Hence, alternative approaches need to be developed to predict maternal-fetal drug exposure throughout pregnancy. To do so, we previously developed and verified a maternal-fetal physiologically based pharmacokinetic model, which can predict fetal exposure to drugs that passively cross the placenta. However, many drugs are actively transported by the placenta (e.g., human immunodeficiency virus protease inhibitors). To extend our maternal-fetal physiologically based pharmacokinetic model to these actively transported drugs, we determined the gestational age-dependent changes in the protein abundance of placental transporters. Total cellular membrane fractions from first trimester (T1; n = 15), second trimester (T2; n = 19), and term (n = 15) human placentae obtained from uncomplicated pregnancies were isolated by ultracentrifugation. Transporter protein abundance was determined by targeted quantitative proteomics using liquid chromatography tandem mass specrometry. We observed that breast cancer resistance protein and P-glycoprotein abundance significantly decreased from T1 to term by 55% and 69%, respectively (per gram of tissue). Organic anion-transporting polypeptide (OATP) 2B1 abundance significantly decreased from T1 to T2 by 32%. In contrast, organic cation transporter (OCT) 3 and organic anion transporter 4 abundance significantly increased with gestational age (2-fold from T1 to term, 1.6-fold from T2 to term). Serotonin transporter and norepinephrine transporter did not change with gestational age. The abundance of bile salt export pump, multidrug resistance-associated protein 1-5, Na+-taurocholate cotransporting polypeptide, OATP1B1, OATP1B3, OCTN1-2, concentrative nucleoside transporter 1-3, equilibrative nucleoside transporter 2, and multidrug and toxin extrusion 1 could not be quantified. These data can be incorporated into our maternal-fetal physiologically based pharmacokinetic model to predict fetal exposure to drugs that are actively transported across the placenta. SIGNIFICANCE STATEMENT: We quantified the protein abundance of key placental uptake and efflux transporters [organic cation transporter (OCT) 3, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)] across gestational ages (first trimester, second trimester, and term) using quantitative targeted proteomics. We observed that the protein abundance of P-gp and BCRP decreased, whereas that of OCT3 increased with gestational age. Incorporating the protein abundance determined in this study into maternal-fetal physiologically based pharmacokinetic model can help us better predict fetal drug exposure to substrates of these transporters.


Fall-related risk factors and osteoporosis in women with rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with an increased risk of osteoporotic fractures. Whilst numerous studies have demonstrated low bone density in RA, few studies have examined the risk of falling, which is another major contributor to the pathogenesis of fractures (particularly hip fractures). The aim of this study was to see if fall risk is increased in women with RA, define high-risk subgroups, and determine what proportion of women have increased risk of hip fracture due to osteoporosis and due to increased fall risk. We performed a case-control study of older women with RA (n = 103) compared with women without RA referred for open access bone densitometry (n = 203). We measured bone density using dual-energy X-ray absorptiometry and fall risk factors (visual acuity, ability to perform standups, and heel-toe walking). More women with RA gave a history of a previous fall compared with controls (54 vs 44%), although this was just short of being statistically significant (difference 10%, 95% CI -2 to 22). Women with RA were more likely to have abnormal heel-toe walking and inability to perform standups compared with controls (P<0.001); however, visual acuity was similar between cases and controls. Femoral neck osteoporosis was found in 31% and increased fall risk in 68% of women with RA. Women with RA who underperformed in heel-toe walking and were unable to do standups had significantly higher ESR, Health Assessment Questionnaire score and tender joint count. RA symptoms/signs localized to the knees and ankles were more likely to be associated with the presence of fall risk factors. Fall-related risk factors predictive of hip fracture are common in women with RA. Fall risk needs to be considered when RA patients are being treated for osteoporosis and further work needs to be done to help reduce the risk of falling and fracture in women with RA.


Protective effects of lipoic acid on chrysene-induced toxicity on Müller cells in vitro.
This study evaluates the toxic effects of chrysene (a component from cigarette smoke) on Müller cells (MIO-M1) in vitro and investigates whether the inhibitor lipoic acid can reverse the chrysene-induced toxic effects. MIO-M1 cells were exposed to varying concentrations of chrysene with or without lipoic acid. Cell viability was measured by a trypan blue dye exclusion assay. Caspase-3/7 activity was measured by a fluorochrome assay. Lactate dehydrogenase (LDH) release was quantified by an LDH assay. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with a 2',7'-dichlorodihydrofluorescein diacetate dye assay. Mitochondrial membrane potential (ΔΨm) was measured using the JC-1 assay. Intracellular ATP content was determined by the ATPLite kit. MIO-M1 cells showed significantly decreased cell viability, increased caspase-3/7 activity, LDH release at the highest chrysene concentration, elevated ROS/RNS levels, decreased ΔΨm value, and decreased intracellular ATP content after exposure to 300, 500, and 1,000 µM chrysene compared with the control. Pretreatment with 80 µM lipoic acid reversed loss of cell viability in 500-µM-chrysene-treated cultures (24.7%, p<0.001). Similarly, pretreatment with 80 µM lipoic acid before chrysene resulted in decreased caspase-3/7 activities (75.7%, p<0.001), decreased ROS/RNS levels (80.02%, p<0.001), increased ΔΨm values (86%, p<0.001), and increased ATP levels (40.5%, p<0.001) compared to 500-µM-chrysene-treated cultures. Chrysene, a component of cigarette smoke, can diminish cell viability in MIO-M1 cells in vitro by apoptosis at the lower concentrations of Chrysene (300 and 500 µM) and necrosis at the highest concentration. Moreover, mitochondrial function was particularly altered. However, lipoic acid can partially reverse the cytotoxic effect of chrysene. Lipoic acid administration may reduce or prevent Müller cell degeneration in retinal degenerative disorders.


Autoradiographic detection of kinin receptors in the human medulla of control, hypertensive, and diabetic donors.
Kinins have been elected to the status of central neuromediators. Their effects are mediated through the activation of two G-protein-coupled receptors, denoted B, and B2. Functional and binding studies suggested that B1 and B2 receptors are upregulated in the medulla and spinal cord of hypertensive and diabetic rats. The aim of this study was to localize and quantify kinin receptors in post-mortem human medulla obtained from normotensive, hypertensive, and diabetic subjects, using in vitro receptor autoradiography with the radioligands [125I]HPP-HOE140 (B2 receptor) and [125I]HPP[des-Arg10]-HOE140 (B1 receptor). Data showed specific binding sites for B2 receptor (0.4-1.5 fmol/mg tissue) in 11 medullary nuclei from 4 control specimens (paratrigeminal > ambiguus > cuneate, gelatinous layer of the caudal spinal trigeminal nucleus > caudal and interpolar spinal trigeminal, external cuneate, solitary tract > hypoglossal > gracile > inferior olivary nuclei). Increased density of B2 receptor binding sites was observed in seven medullary nuclei of four hypertensive specimens (paratrigeminal > external cuneate > interpolar and caudal spinal trigeminal, gracile, inferior olivary > hypoglossal nuclei). B2 receptor binding sites were seemingly increased in the same medullary nuclei of two diabetic specimens. Specific binding sites for B1 receptor (1.05 and 1.36 fmol/mg tissue) were seen only in the inferior olivary nucleus in two out of the ten studied specimens. The present results support a putative role for kinins in the regulation of autonomic, nociceptive, and motor functions at the level of the human medulla. Evidence is also provided that B2 receptors are upregulated in medullary cardiovascular centers of subjects afflicted of cardiovascular diseases.


A non-canonical role of the p97 complex in RIG-I antiviral signaling.
RIG-I is a well-studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181. Viral infection significantly strengthens the interaction between RIG-I and the p97 complex by a conformational change of RIG-I that exposes the CARDs and through K63-linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG-I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy.


Diet Quality and Physical Fighting Among Youth: A Cross-National Study.
The predictors of engaging in physical violence appear to be quite diverse, covering an array of social and psychological risk factors. The present study expands upon this literature by exploring the link between diet quality and physical fighting during early adolescence using cross-national data from the 2005/2006 Health Behaviors of School Children (HBSC) survey. The results reveal that the rate of physical fighting was 40% higher among youths with lower quality diets, whereas the odds of frequent physical fighting were 68% higher, relative to youths with better diets. Ancillary analyses reveal that (a) the link between diet quality and physical fighting was significantly larger among females and (b) significant associations between diet quality and physical fighting were detected in 38 of the 40 countries examined. Strategies designed to improve diet quality among youth may have the added benefit of reducing the likelihood of physical fighting and its negative sequelae.


Temperature-Dependent Modulation of Short-Wave-Infrared Light Transparency Based on Associated Structures of a Liquescent Nickel(III) Complex.
A liquescent bis(malononitriledithiolato)nickel(III) complex with a bis(methoxyethyl)imidazolium cation, 1[Ni(mnt)2 ], exhibits three-stage thermochromic modulation of transparency/absorption in the short-wave-infrared (SWIR) region (1000-2500 nm), driven by associated structural changes. Upon heating, the electronic spectra of 1[Ni(mnt)2 ] in the SWIR region shift to shorter wavelengths accompanying with the solid-liquid phase transition at 76 °C. Further heating to over 109 °C induces a second transition of the electronic spectra, characterized by a blue-shift of the SWIR absorption in the liquid phase. The results of temperature-dependent electronic spectra and magnetic susceptibility indicated that the thermochromic changes can be attributed to the two-step dissociation of the associated structures of [Ni(mnt)2 ]- , occurring during the solid-liquid phase transition and the shift of dimer-monomer equilibrium in the liquid state. These changes can be visualized using an SWIR imaging camera under appropriate SWIR lights.


Improved photoacoustic images via wavefront shaping modulation based on the scattering structure.
Multispectral optoacoustic tomography (MSOT) has become the dominant technical solution for photoacoustic imaging (PAI). However, the laser source of fiber output in the current MSOT method is typically a TEM00 Gaussian beam, which is prone to artifacts and incomplete due to the uneven distribution of the irradiated light intensity. Here, we propose a novel method to improve the quality of photoacoustic image reconstruction by modulating the wavefront shaping of the incident laser beam based on the designed scattering structure. In the experiment, we add the designed scattering structure to the current hemispherical photoacoustic transducer array device. Through experiments and simulations, we investigate and compare the effects of different scattering structures on laser intensity modulation. The results show that an ED1-C20 diffusion structure with a scattering angle of 20 degrees has the most effective modulation of the beam intensity distribution. And we choose gold nanoparticles of 50-100 nanometers (nm) diameters and index finger capillary vessels respectively as the medium of PAI. We obtain the highest ratio of PAI area increases of gold nanoparticles and index finger to devices compare without scattering structure is 29.69% and 634.94%, respectively. Experimental results demonstrate that our method is significantly higher quality than traditional methods, which has great potential for theoretical application in medical PAI.


Smoke-free laws and direct democracy initiatives on smoking bans in Germany: a systematic review and quantitative assessment.
Germany's 16 states regulate smoking differently within health protection principles laid down in the federal law. All state smoke-free laws in Germany have undergone at least one change since taking effect. We systematically review federal and state laws regulating smoking, as well as petitions, popular initiatives and referenda that aimed at changing statutory smoking bans. Data generated through the systematic review were correlated with state smoking rates. The protection from the dangers of secondhand smoke is the primary motive for smoking bans in Germany. The first smoke-free laws affecting smoking in pubs, restaurants and several other public places were introduced in 2007. In 2008, the Federal Constitutional Court of Germany ruled in a leading decision on the smoke-free laws of two states that some common smoking ban exemptions of the introduced smoke-free laws violate the basic right to freely exercise a profession and mandated revisions. All states but Bavaria and Saarland, whose smoking bans were more and less comprehensive than those judged by the constitutional court, respectively, needed to change the smoking ban exemptions to reconcile their smoke-free laws with the constitution. Direct democracy initiatives to change smoking bans were only successful in Bavaria in 2010, but a total of 15 initiatives by citizens' or interest groups attempted to influence non-smokers protection legislation through direct democratic procedures. Early ratification of a smoking ban in a federal state correlates with a higher reduction in the smoking rate from 2005 to 2009 (Spearman's ρ = 0.51, p = 0.04). The federal government structure and direct democratic participation in smoke-free legislation in Germany has produced a diversity of local smoking bans and exemptions.


Karwinaphthopyranones from the fruits of Karwinskia parvifolia and their cytotoxic activities.
The new 2-acetyl-8-methoxynaphthol (1) and five new "dimeric" napthopyranones, karwinaphthopyranones A1 and A2 (2 and 3) and karwinaphthopyranones B1-B3 (4-6), possessing a methoxy group at C-5', were isolated together with four other known compounds from the dried fruits of Karwinskia parvifolia. The structures of compounds 2-6 were determined by spectroscopic data interpretation. Cell culture assays showed that some of these compounds possess antiproliferative activities in representative human cancer cell lines, with half-maximal growth inhibitory concentrations in the micromolar range.


Effect of Epididymal Spermatozoa of Local Iraqi Goat on in vitro Fertilization and Evolution of Embryos.
In vitro fertilization (IVF) has been considered one of the greatest improvements in livestock science and production. Epididymal spermatozoon is a valuable gamete source obtained from slaughtered animals, and it has great importance in livestock IVF. This study aimed to create caprine embryos in Baghdad using local Iraqi goats. Ovaries were obtained from 50 female local goats at the Al-shu'alah abattoir. The ovaries were transported to the laboratory in physiological saline solution at 38°C. After oocyte recovery from the mature antral follicle, the oocytes with grades A or B were used for in vitro maturation (IVM). Moreover, 10 testicles were obtained from slaughtered adult goats, and the sperm was recovered from the caudal epididymis. All the stage-specific culture mediums were incubated at 39°C with 5% CO2 and 90% relative humidity. In this study, embryonic development on a 24-h basis was evaluated and in vitro culture media was replaced 50% of the volume every day for nine days with fresh media until an enlarged or hatched blastocyst appeared. The recorded data showed that the mean size of the large follicles was 6.23±1.34 mm, while the small follicles were in the mean size of 3.10±0.62. On the other hand, the results showed a significant increase in the oocyte recovery rate from the large size follicle (81.22%), compared to the small size follicle (62.67%). The recorded data showed that the total number of retrieved oocytes with grades A and B was 290 (79.5%) . The recorded data showed that 50.1% of these oocyte cohorts had reached metaphase II (145/290). Furthermore, 45.45% of the recovered oocytes by aspiration from large follicles were developed to the blastocyst stage, compared to 25% of recovered oocytes from the small follicles reaching the same developmental stage (blastocyst). On the other hand, the recorded data showed that the oocyte recovery method had a great influence on the oocyte competence regardless of the follicle size. The results revealed that the number of recovered oocytes by aspiration was greater than slicing. In conclusion, the results approved that the slicing method could be considered a safe and more efficient method in oocyte recovery from the slaughtered animals, compared to the aspiration method. On the other hand, according to the findings, the epididymal spermatozoa from local Iraqi goats are a reliable source of oocytes for IVF and in vitro conversion.


Chemoprotective effects of Zataria multiflora against genotoxicity induced by cyclophosphamide in mice bone marrow cells.
The preventive effective of Zataria multiflora (ZM) extract was investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide (CP). Mice were orally (gavaged) pretreated with solutions of ZM extract prepared at 3 different doses (50, 100, and 200 mg/kg body weight) for 7 consecutive days. They were injected with CP (50 mg/kg body weight) on the seventh day of treatment and killed after 24 hours for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of PCE/(PCE + NCE), where PCE refers to polychromatic erythrocyte, and NCE refers to normochromatic erythrocyte. All 3 doses of extract significantly reduced MnPCEs induced by CP (P < .0001). Zataria extract at a dose of 200 mg/kg body weight reduced MnPCEs 7.8 fold and also completely normalized the PCE/ (PCE + NCE) ratio. Administration of ZM inhibited bone marrow suppression induced by CP. Zataria extract exhibited concentration-dependent antioxidant activity on 1, 1-diphenyl 2-picryl hydrazyl free radical and lipid peroxidation. It appeared that ZM with antioxidative activity reduced the oxidative stress and genotoxicity induced by CP in mouse bone marrow cells.


Hormone-based therapies in MS.
It is well established in multiple sclerosis (MS) that the frequency of relapses decreases in late pregnancy, but increases in the post-partum period. This protective effect is probably due to hormonal and immune response changes induced by pregnancy. Oestrogens may be responsible, at least in part, for this protective effect. The potential use of oestrogens as therapy for MS is discussed.


Adolescent and Parent Experience of Care at a Family-Based Treatment Service for Eating Disorders.
Incorporating consumer perspectives is an important but often overlooked opportunity to optimize treatment engagement and outcomes for adolescents with eating disorders. This study explored the experience of care of adolescents and their parents at a multidisciplinary specialist eating disorders service providing family-based treatment (FBT) as first-line treatment. Eighty-five adolescents and 145 parents who completed FBT at the service between 2013 and 2015 were surveyed in 2017 about their experience of care. A study-designed survey asked respondents to rate on Likert scales their experience of service access, intake assessment, education, support, interactions with the treatment team, recovery, and the discharge process. Open-ended comments on helpful and unhelpful aspects of the service provided further context on the ratings. Overall families were very positive about their experience, particularly in regard to assessment, education, interactions with the team, and achieving physical health. Although parents tended to be more satisfied, adolescents also held the service in high regard. Some areas were identified that could be improved, including treatment delays, carer support, therapeutic alliance, and preparation for discharge. Surveying families about their experience of care provides an important opportunity to identify service strengths as well as services gaps. The results indicated several areas that specialist eating disorder services could focus on to ensure that the services provided, including FBT, fully meet the needs of families and optimize adolescents' treatment experiences.


Predictors of asthma-related health care utilization and quality of life among inner-city patients with asthma.
Asthma morbidity and mortality are highest among minority inner-city populations. To identify factors associated with acute health care resource utilization and asthma-related quality of life among high-risk, minority patients with asthma. We interviewed a prospective cohort of 198 adults hospitalized for asthma in an inner city hospital over a period of 1 year. Detailed information about sociodemographics, asthma history, access to care, asthma medications, and self-reported allergy to aeroallergens was collected at baseline. Data on resource utilization (emergency department visits and hospital admissions for asthma) and asthma-related quality of life were obtained at 6 months after discharge. Multivariate analyses were used to identify predictors of resource utilization and quality of life. The mean age of patients was 49.9 +/- 17.4 years, 78% were women, and 97% were nonwhite. At 6 months, 49% of patients had an emergency department visit or hospitalization. In multivariate analysis, adjusting for age, sex, medication regimen, and asthma severity, patients with a physician in charge of their asthma care had lower odds of resource utilization (odds ratio, 0.4; P=.03). Conversely, a self-reported history of cockroach allergy was associated with greater utilization (odds ratio, 2.3; P=.05). Asthma-related quality of life was worse among patients who spoke mostly Spanish or who reported allergy to cockroaches (P < .004). Lack of an established asthma care provider, language barriers, and self-reported allergy to cockroaches are associated with higher resource utilization and worse quality of life among minority, inner-city patients with asthma. Interventions targeting these factors may lead to better outcomes among these patients.


Predicting the Conditions for Homeotropic Anchoring of Liquid Crystals at a Soft Surface. 4-n-Pentyl-4'-cyanobiphenyl on Alkylsilane Self-Assembled Monolayers.
We have studied, using atomistic molecular dynamics simulations, the alignment of the nematic liquid-crystal 4-n-pentyl-4'-cyanobiphenyl (5CB) on self-assembled monolayers (SAMs) formed from octadecyl- and/or hexyltrichlorosilane (OTS and HTS) attached to glassy silica. We find a planar alignment on OTS at full coverage and an intermediate situation at partial OTS coverage because of the penetration of 5CB molecules into the monolayer, which also removes the tilt of the OTS SAM. Binary mixtures of HTS and OTS SAMs instead induce homeotropic (i.e., perpendicular) alignment. A comparison with the existing experimental literature is provided.


Revisiting ischemia and reperfusion injury as a possible cause of necrotizing enterocolitis: Role of nitric oxide and superoxide dismutase.
The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered a major contributing factor. Nitric oxide (NO) and superoxide dismutases (SODs) have been shown to protect bowel from I/R injury. This study aims to assess (1) the ability of premature intestine to resist I/R injury compared with mature intestine and (2) the possible role of NO and SODs in modulating such response. Intestines from 5 groups of rats (n = 6 for each study group) were studied: (1) premature, gestational age 20 days; (2) premature, gestational age 22 days; (3) full-term, newborn; (4) infant, day 15; (5) infant, day 30. (1) The degrees of I/R injury after 0, 30, 60, 90 and 120 minutes, respectively, of ischemia and 25 minutes of I/R were assessed histologically by a pathologist who was unaware of the operative details. (2) Tissue NO and copper levels were measured by electroparamagnetic resonance (EPR) study; and nitric oxide synthases, copper zinc (CuZn) SODs and manganese (Mn) SODs were examined immunohistochemically. (3) and (4) I/R injury was assessed in rats that had received intraperitoneal injections of L-arginine (NO donor) and L-NAME (NO antagonist), respectively. For premature (1,2), newborn (3) and mature (4,5) intestines, grades of injury at maximum I/R period studied (120 minutes of ischemia, 25 minutes of reperfusion) were 0, 0, and 3, respectively (P <.05); NO levels were 1 u +/- 1.5, 3 +/- 2.5, and 22 u +/- 3.5, respectively (P <.05); Cu levels were 150 u +/- 15, 200 u +/- 41 and 12 u +/- 2, respectively (P <.05); NOS in intestines were +, +, +++ and CuZnSODs were ++, +++, +, respectively; and MnSODs were +++, ++, -, respectively. No change in NO levels was detected in groups (1), (2), or (3) after L-arginine and L-NAME injections. Premature rat intestine is highly resistant to I/R injury, which may indicate that I/R alone, in the absence of other predisposing factors (eg, bacterial colonization) may not be sufficient in causing NEC. Nitric oxide does not have a protective role for immature and newborn intestines in I/R as in mature intestine. The high level of SODs of the immature and newborn intestine may play an important role in its high resistance to I/R injury.


Handedness, eyedness, and crossed hand-eye dominance in male and female patients with migraine with and without aura: a pilot study.
The possible relationships of migraine to left-handedness and left-eyedness, as well as sex and aura-related differences, were examined. 146 migraine patients (M age=32.1 yr., SD=9.5) and 141 controls (M age=30.0 yr., SD=9.3) participated. Hand preference was assessed by the modified version of the Edinburgh Handedness Inventory. Ocular dominance was measured by means of the near-far alignment test. Migraine diagnoses were made on the basis of criteria provided from the International Headache Society. In the overall sample and in women, left-handedness and left-eyedness were not significantly correlated with migraine. In men, the incidence of left-handedness and left-eyedness were significantly higher in patients than in controls. The presence of aura in patients with migraine was significantly associated with the incidence of left-eyedness and crossed hand-eye dominance, but not handedness, for the total sample and women. These results suggest that there may be a tendency towards anomalous dominance, especially left-eyedness, in migraine patients particularly those with aura.


[Biomolecules transfection into animal cells].
In vitro cell culture technology allowed examining many metabolic processes. Transfection tool of macromolecules (especially DNA) into cells permits testing gene and noncoding sequences function. Transfection procedures are widely available for researchers nowadays. This paper describes mostly used transfection techniques as well as the latest achievements in the field.


Hepatitis C and hospital outcomes in patients admitted with alcohol-related problems.
Alcohol is known to act synergistically with chronic hepatitis C virus (HCV) infection to cause liver disease; however, their combined effect on outcomes in acutely hospitalized patients is less clear. We examined the impact of HCV infection on hospital mortality and length of stay among hospitalized patients with alcohol abuse problems. We retrospectively identified 6354 admissions to an urban, public hospital between July 1996 and January 2002 with discharge diagnoses related to alcohol dependence or abuse. Hepatitis C diagnosis and other information were extracted from a clinical database and tested for associations with death and length of hospital stay using multivariable regression techniques. The prevalence of diagnosed HCV infection in this sample of patients with alcohol abuse was 15%. Patients with HCV were about twice as likely to die during hospital admission (4.4 vs. 2.4%; P-value < 0.01), and there appeared to be a trend toward increased mortality even after adjustment for demographics, medical service, homelessness and comorbidities (fully adjusted OR 1.41; 95% CI: 0.97-2.04). Length of stay was significantly longer for patients with HCV (19% longer; 95% CI: 12-27% after adjustment) than those without. Patients admitted to the hospital with alcohol-related diagnoses have longer hospital stays and are more likely to die in hospital if they have a diagnosis of HCV.


Current results of open revascularization for chronic mesenteric ischemia: a standard for comparison.
Questions remain concerning the optimal site of graft origin and the extent of revascularization necessary to achieve excellent results for chronic mesenteric ischemia (CMI). Endovascular therapy also is performed for CMI. These factors prompted us to review our results to provide a current standard. Ninety-eight patients who underwent operation for CMI from 1989 to 1998 were reviewed. Patients with acute ischemia and arcuate ligament syndrome were excluded. Seventy-six women (78%) and 22 men (22%), with an average age of 66 years (range, 36 to 87 years), participated in the study. Abdominal pain was present in 95 patients (97%), and weight loss in 92 patients (94%). The superior mesenteric artery was severely diseased (70% to 99% stenosis or occlusion) in 90 patients (92%), the celiac artery in 81 patients (83%), and both arteries in 76 patients (78%). Bypass grafts were performed in 91 patients (93%), 77 antegrade and 14 retrograde. Of the other seven patients, five had endarterectomies, one reimplantation, and one patch angioplasty. Multivessel reconstruction was performed in 79 patients (81%), and single-vessel reconstruction in 19 (19%). Twelve patients had concomitant aortic reconstruction. Three early graft thromboses were seen. Five hospital deaths occurred (5.1%); one case had concomitant aortic reconstruction (1/12 versus 4/86; P = not significant). All five patients who died were older than 70 years (5/41 versus 0/57; P =.011). The median follow-up period was 1.9 years (range, 0 to 9.6 years). Follow-up was complete in all survivors. The 1-year, 5-year, and 8-year survival rates were 83%, 63%, and 55%, respectively. These rates were worse than the rates of the age-matched/gender-matched control subjects (P <.001). Survival was worse in patients greater than 70 years of age (P =.0013). Survival was unaffected by the number of vessels revascularized. The patients with retrograde grafts had decreased median survival rates (4.0 versus 5.7 years; P =.026), but they were older (75 versus 65 years; P =.0013). The 1-year and 5-year symptom-free survival rates were 95% and 92%, respectively. Symptoms recurred in six patients (6%): four had recurrent stenosis/occlusion and two had patent grafts. Symptom-free survival was unaffected by the number of vessels revascularized or by graft orientation. Operation for CMI was successful for most patients, with low operative mortality and excellent long-term relief of symptoms. Selective concomitant aortic procedures did not increase mortality rates. The rate of symptomatic recurrences was not different for single-vessel versus multiple-vessel reconstructions or for antegrade versus retrograde grafts. Patients older than 70 years had increased operative mortality and decreased survival rates. Endovascular therapy may be appropriate for this subset of patients.


Social participation experiences of older adults with an early-onset physical disability: a systematic review protocol.
The objective of this review is to assess and synthesize the available qualitative evidence on the experiences of social participation of older adults with an early-onset physical disability. Understanding the experiences of social participation among older adults with a physical disability acquired earlier in life can guide the development of interventions and policies. It will also help with fostering meaningful community participation and aid in improving the quality of their social participation. This review will consider primary studies that explore the experiences of social participation of older adults with an early-onset physical disability. The review will focus on qualitative data, including methods such as phenomenology, grounded theory, ethnography, action research, and feminist research. Studies in French or English will be considered for inclusion, and there will be no limitation on publication dates. A keyword search strategy will be carried out in MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), Web of Science, and The Cochrane Library. ProQuest Dissertations and Theses (ProQuest) will be searched for unpublished articles. Two independent reviewers will perform the screening and inclusion process, assess the quality of the evidence, and complete data extraction. The JBI approach to critical appraisal, study selection, data extraction, and data synthesis (meta-aggregation) will be used. The ConQual approach will be used to establish confidence in the synthesized findings. PROSPERO CRD42022371027.


A model-based quantification of action control deficits in Parkinson's disease.
Basal ganglia dysfunction in Parkinson's disease (PD) is thought to generate deficits in action control, but the characterization of these deficits have been qualitative rather than quantitative. Patients with PD typically show prolonged response times on tasks that instantiate a conflict between goal-directed processing and automatic response tendencies. In the Simon task, for example, the irrelevant location of the stimulus automatically activates a corresponding lateralized response, generating a potential conflict with goal-directed choices. We applied a new computational model of conflict processing to two sets of behavioral data from the Simon task to quantify the effects of PD and dopaminergic (DA) medication on action control mechanisms. Compared to healthy controls (HC) matched in age gender and education, patients with PD showed a deficit in goal-directed processing, and the magnitude of this deficit positively correlated with cognitive symptoms. Analyses of the time-course of the location-based automatic activation yielded mixed findings. In both datasets, we found that the peak amplitude of the automatic activation was similar between PD and HC, demonstrating a similar degree of response capture. However, PD patients showed a prolonged automatic activation in only one dataset. This discrepancy was resolved by theoretical analyses of conflict resolution in the Simon task. The reduction of interference generated by the automatic activation appears to be driven by a mixture of passive decay and top-down inhibitory control, the contribution of each component being modulated by task demands. Our results suggest that PD selectively impairs the inhibitory control component, a deficit likely remediated by DA medication. This work advances our understanding of action control deficits in PD, and illustrates the benefit of using computational models to quantitatively measure cognitive processes in clinical populations.


Biodegradation of 17 β-estradiol by Serratia marcescens and Stenotrophomonas tumulicola co-culture isolated from a sewage treatment plant in Upper Egypt.
17 β-estradiol (E2) is an important pollutant of the aquatic system. It is responsible for sexual disruptions in the majority of aquatic organisms. This study aimed to search for bacteria with high potential degradation of E2 as an important method for bioremediation. Sewage water samples were collected and treated to isolate bacterial strains which were identified by conventional methods and 16S ribosomal RNA gene sequence analysis. The biodegradation of E2 by the isolated strains was evaluated under different environmental conditions. Two bacterial strains were recovered from sewage water samples and identified as Stenotrophomonas tumulicola and Serratia marcescens, (named ASc2 and ASc5 respectively). Co-culture of the two strains showed biodegradation of approximately 93.6 % of E2 (50 mg. L-1) within 48 hours. However, the biodegradation capacity of the same E2 concentration was 69.4% and 71.2% for ASc2 and ASc5 each alone, respectively. The optimum cultivation conditions for efficient E2 biodegradation by co-culture were 5% (v/v) inoculation volume with 50 mg. L-1 of E2 as the initial concentration at pH 7 and 30°C within 48 hours inoculation period. This study detected new bacterial strains that are capable of rapid degradation of estrogen as an environmental pollutant.


Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis.
In this study, we showed that curcumin treatment resulted in activation of Chk1-mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin-induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin-resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1-mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin.


[Callus distraction for progressive lengthening of the capitate bone after resection of the lunate bone in stage III lunate malacia. Surgical technique and 1 year results].
Inspite of the excellent subjective judgement and functional results of Graner's operation in case of Kienbock's disease stage III, this technique is rarely used nowadays because of its high rate (20 to 30%) of disturbed fracture healing due to impaired blood supply. To avoid the risk of complete devascularization in the capitate region, we are using the callotaxis lengthening technique of Ilizaron, carrying out a segmental shifting. After percutaneous temporary SC- or STT-arthrodesis with the scaphoid in the horizontal or high position, the lunate is completely resected using a dorsal approach. Osteotomy of the capitate is carried out at the corpus-collum interval in order to disturb a minimum of the vascular supply to the bone. Seven to ten days postoperatively, distraction is started with a rate of 1 min/day. The desired distraction length is accomplished, when the capitate articular surface fits perfectly into the curvature of the proximal row articular surface. In order to reduce or prevent soft tissue related complications during the consolidation period, the external distractor is replaced by two percutaneous Kirschner-wires. The consolidation period takes twice as long as the distraction period. Since November 1993, fourteen patients presenting a stage III Kienböck's disease have been treated by this new technique. The operative technique, postoperative care, as well as the potential and real complications are described and illustrated by one clinical case.


Effect of alpha 1-adrenoceptor blockade on maximal VO2 and endurance capacity in well-trained athletic hypertensive men.
The effect of alpha 1-adrenoceptor blockade (doxazosin, 4 mg daily) on maximal VO2 and physical endurance capacity in 16 mildly hypertensive, athletic men was investigated in a randomized, placebo-controlled, double-blind, two-period of 4 weeks, cross-over study. The maximal workload obtained during graded bicycle ergometer exercise and the corresponding maximal VO2 were reduced by 16 +/- 3 W (mean +/- SE), (P = .00003) and 3 +/- 1 mL/(kg.min) (P = .0004), respectively, on doxazosin compared with placebo. The running time on a 5000 m track increased by 43 +/- 12 sec on doxazosin (P = .04). Heart rate was unchanged during the running session. Systolic blood pressure was reduced by 9 +/- 4.1 mm Hg (P = .04) immediately after finishing 5000 m. Six subjects reported side effects from doxazosin (headache, fatigue, and leg pain). Thus, antihypertensive treatment with alpha 1-selective adrenoceptor blockade moderately, but significantly, reduces maximal O2 consumption and high intensity physical endurance capacity in mildly hypertensive athletic men. Significantly reduced systolic blood pressure and unchanged heart rate immediately after running, combined with unchanged heart rate during the race may, however, suggest a safer exercise performance.


Functional maturation of nasal mucosa: role of secretory immunoglobulin A (SIgA).
Secretory IgA (SIgA) plays an important role in defending the mucous membranes of the upper respiratory airways from common infection. Studying and comparing the values and the daily variation of SIgA in nasal secretion could explain the largest number of upper respiratory infection, especially in children.Moreover, the ELISA dosage of SIgA in nasal secretion, sampled by cotton swabs positioned between septum and middle turbinate for 20 minutes every 4 hours 5 times in a day, can be easily performed and shows significant differences between the healthy child and the healthy adult.Nasal secretion SIgA mean value is lower in the healthy child than in the healthy adult. Circadian variation for healthy child showed the highest value at 7.00 a.m., while in adult the highest value was at 4.00 a.m.These knowledge on SIgA may help to explain the highest number of upper airway infection during childhood and clarify the physiological cycle of production. Thus, in performing a SIgA dosage the time of sample must be considered and preferably it should be made at a standardized time of the day.


Application of chimeric glucanase comprising mutanase and dextranase for prevention of dental biofilm formation.
Water-insoluble glucan (WIG) produced by mutans streptococci, an important cariogenic pathogen, plays an important role in the formation of dental biofilm and adhesion of biofilm to tooth surfaces. Glucanohydrolases, such as mutanase (α-1,3-glucanase) and dextranase (α-1,6-glucanase), are able to hydrolyze WIG. The purposes of this study were to construct bi-functional chimeric glucanase, composed of mutanase and dextranase, and to examine the effects of this chimeric glucanase on the formation and decomposition of biofilm. The mutanase gene from Paenibacillus humicus NA1123 and the dextranase gene from Streptococcus mutans ATCC 25175 were cloned and ligated into a pE-SUMOstar Amp plasmid vector. The resultant his-tagged fusion chimeric glucanase was expressed in Escherichia coli BL21 (DE3) and partially purified. The effects of chimeric glucanase on the formation and decomposition of biofilm formed on a glass surface by Streptococcus sobrinus 6715 glucosyltransferases were then examined. This biofilm was fractionated into firmly adherent, loosely adherent, and non-adherent WIG fractions. Amounts of WIG in each fraction were determined by a phenol-sulfuric acid method, and reducing sugars were quantified by the Somogyi-Nelson method. Chimeric glucanase reduced the formation of the total amount of WIG in a dose-dependent manner, and significant reductions of WIG in the adherent fraction were observed. Moreover, the chimeric glucanase was able to decompose biofilm, being 4.1 times more effective at glucan inhibition of biofilm formation than a mixture of dextranase and mutanase. These results suggest that the chimeric glucanase is useful for prevention of dental biofilm formation.


Emodin relieves hypoxia-triggered injury via elevation of microRNA-25 in PC-12 cells.
Emodin (EMO) possesses extensive pharmacological activities, which has been proven to exert the protective impact in diverse nervous system diseases. Nonetheless, whether EMO emerges a neuro-protective activity in hypoxic-evoked ischemic brain injury is still further probed. The intention of the research is to disclose whether EMO emerges neuro-protective activity in hypoxic-evoked ischemic brain injury. PC-12 received hypoxia administration, and then cell viability, apoptosis and autophagy were estimated. After EMO disposition, the above-involved cellular processes were evaluated again. MiR-25 functions in EMO-affected cells were also estimated. The interrelation between miR-25 and neurofilament light-chain polypeptide gene (NEFL) and the conceivable roles of NEFL in hypoxia-disposed cells were investigated. The latent mechanism was uncovered by mTOR and Notch pathways determination. Hypoxia triumphantly triggered apoptosis and autophagy, but EMO repressed these functions in PC-12 cells. Increased miR-25 was induced by EMO, and inhibited miR-25 abated the impacts of EMO on hypoxia-disposed PC-12 cells. NEFL as a neoteric target gene of miR-25 was predicated, and overexpressed NEFL annulled the functions of EMO in hypoxia-injured cells. EMO activated mTOR and Notch pathways through repressing NEFL. The investigations corroborated that EMO weakened hypoxia-triggered injury via elevating miR-25 by targeting NEFL in PC-12 cells.


The therapeutic effects of tenidap in canine experimental osteoarthritis: relationship with biochemical markers.
To define the dose-response relationship of the therapeutic effects of tenidap in experimental osteoarthritis (OA) and relate this to the effects on interleukin 1 (IL-1) and metalloprotease activity. The anterior cruciate ligament of the right knee joints of 22 mongrel dogs were sectioned (ACLS) through a stab wound. Seven dogs received no treatment, 5 were treated with oral omeprazole (20 mg/day), another 5 were treated with oral tenidap (1.5 mg/kg bid) plus omeprazole (20 mg/day), and 5 received tenidap (0.5 mg/kg bid) plus omeprazole (20 mg/day). The dogs received medication for 8 weeks beginning 4 weeks after surgery. All dogs were killed 12 weeks after surgery, except for those in the first group, which were sacrificed at 4 weeks. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin, collagenase, and gelatinase activities were measured in cartilage and synovial membrane. Also, the level of IL-1 activity was measured in the synovial fluid. Dogs treated with tenidap at both 1.5 and 0.5 mg/kg bid exhibited a reduction in the size of osteophytes (2.25 +/- 0.30 mm, 1.70 +/- 0.65 mm, respectively) compared to the 12 weeks OA group (3.55 +/- 0.94 mm). Tenidap also significantly decreased the size and/or grade or cartilage macroscopic lesions on both condyles and plateaus. This reduction was more pronounced in dogs treated with the higher drug dose. The histological severity of cartilage lesions on femoral condyles was reduced for both tenidap doses used and significance (p < 0.04) reached for the 1.5 mg/kg bid tenidap treated dogs. Tenidap markedly and significantly reduced the level of metalloprotease activity for all 3 enzymes tested in synovial membrane (stromelysin, p < 0.03; collagenase, p < 0.02; gelatinase, p < 0.03) and in cartilage (stromelysin, p < 0.02; collagenase, p < 0.02; gelatinase, p < 0.03) with greater reduction, in general, in dogs treated with the higher dose of tenidap. IL-1 activity was significantly reduced (p < 0.02) only in animals treated with tenidap at 1.5 mg/kg bid. This study confirms that tenidap is an effective anti-osteoarthritic drug in this ACLS model where therapy was begun 4 weeks after surgery. We have defined doses that gave graded therapeutic effects, and under these conditions the effectiveness coincided with the suppression of IL-1 and metalloprotease activity, processes known to play a major role in the pathophysiology of OA lesions.